We have cloned the lysosomal a-mannosidase from Trypanosoma cruzi that has been proposed to be involved in the turnover of the cell-surface lipopeptidophosphoglycan (LPPG) and LPPG-related structures during developmental stage changes in the parasite. This enzyme is induced in the parasite and has highest activity levels in the epimastigotes. A distinctive feature of this enzyme is its size. By comparison to the other lysosomal enzymes in mammalian systems, the T. cruzi lysosomal a-mannosidase is ~50% smaller, yet the polypeptide sequence retains a strong sequence similarity to the mammalian and slime mold lysosomal a-mannosidases. Further characterization of this enzyme should yield insights into the structural features of the Class II a-mannosidases that are necessary for catalysis.